Читать книгу Protocols for High-Risk Pregnancies - Группа авторов - Страница 112

Hemoglobin A, the normal adult form of hemoglobin, is comprised of two alpha and two beta globin chains. Sickle cell disorders are due to an abnormal combination of hemoglobin structural variants including S, C, or E, or one of these variants coupled with a thalassemic mutation. Such variant sickle cell hemoglobins are produced by single nucleotide alterations in the beta globin chain. Alpha‐thalassemia is due to deletion of two (alpha‐thalassemia minor), three (hemoglobin H disease), or four (alpha‐thalassemia major or hemoglobin Barts) of the four copies of the alpha globin gene which results in decreased or absent production. Notably, a cis‐mutation of alpha globin, defined as deletion of both alpha globin copies on the same chromosome, is more common among those of Southeast Asian background and is more likely to result in hemoglobin H disease or alpha‐thalassemia major. In contrast, a transmutation where a single deletion is found on each chromosome (more common among those of African American race) is less likely to result in a fetus with alpha‐thalassemia major. Beta‐thalassemia minor occurs among heterozygotes with a beta globin gene mutation resulting in deficient production; beta‐thalassemia major is due to homozygosity or compound heterozygosity of a mutated beta globin gene that causes decreased to absent production.

When the production of alpha or beta globin is impaired, increasing quantities of variant hemoglobin, such as hemoglobin F or A₂, are produced relative to the production of normal hemoglobin A, causing the variation in disease states described above.